Thousands of people of all ages are admitted to hospitals daily because of the malfunction of a vital organ. Until very recently, it was believed that the only solutions to treat these cases were organ transplants or replacements by totally artificial parts.

There are several treatment options for organ failure or tissue loss ? transplants, reconstructive surgery, artificial prosthesis or mechanical devices (kidney dialyzers, prosthetic hip joints, mechanical heart valves), but unfortunately, they are imperfect. There's a declining availability of organs, there's the need for multiple surgery in the case of autografts and mechanical devices do not have the capacity to perform all functions of an organ. Prosthetic replacements present risks such as thrombosis, an increased susceptibility to infection, limited durability, need for reoperations.

In this context, the emergence of the science called tissue engineering is more than just salutary. The purpose of tissue engineering is to create tissues in culture for use as replacement tissues for damaged body parts. Within the past 10 years, the creation of bioartificial tissues has achieved a series of successes.

The science of tissue engineering combines the principles of bioengineering, cell transplantation, hematology ad those of material science/engineering, for the unique goal of generating bioartficial tissues and organs. Skin, cartilage and bone have been synthesized in the laboratory, and success has been predicted in the creation of blood vessels, blood and organs such as heart, lungs, pancreas, and liver. Attempts have been made to create artificial corneas, intestines and heart valves. Bladders have been bioengineered and implanted in dogs, with total success.

The process generally comprises of the isolation of cells from a patient and their growth on three-dimensional templates or scaffolds (matrices), under the conditions necessary for them to develop into functional tissue. Then, the tissue-biomaterial construct is implanted into the patient. The biomaterial gradually absorbs, ensuring that only the natural tissue remains in the body, having acquired the shape of the material. This process completed, the bioartificial tissue becomes structurally and functionally integrated into the body.

The quality of the scaffold is essential. It has to be extremely malleable, completely biodegradable, immunologically inert to avoid rejection, and it has to provide the perfect conditions for cell repopulation (to deliver and allow delivery of biochemical factors and vital cell nutrients). Porosity and pore size is important for cell seeding and for the diffusion of nutrients.

Scaffolds may be constructed out of synthetic materials(such as PLA ? polylactic acid, a polyester which degrades within the body to form lactic acid, PGA ? polyglicolic acid, PCL ? polycaprolactone) or of natural materials: proteic materials (collagen, fibrin) or polysaccharidic materials (chitosan, glycosaminoglycans). Development of new materials is one of the focus points of future research.

The seeding of appropriate cells can be performed both in the laboratory and in-vivo. Repopulation of the scaffolding can occur either passively or actively (in which cells are ?forced � onto the matrix). Tissue growth outside the body implies placing human cells on the scaffold inside a bioreactor ? a device that simulates human body conditions. The cells start secreting growth factors and form a living tissue.

The sources and types of cells used vary. Cells can be obtained from the same patient they are intended for, by a small tissue biopsy (autologous cells). Autologous cells are preferred as they avoid an immune response in the patient after reimplantation and cause no pathogenic transmission problems. However, there may be problems with using this type of cells, such as unavailability, in cases of a genetic disease of the patient, of very ill or elderly persons or of patients suffering from severe burns. Donor site infection and cases of severe pain are two other concerns in harvesting these cells, as well as the fact that culturing of autologous cells usually takes considerable time.

Recently, mesenchymal stem cells from bone marrow and fat have been preferred. Stem cells are primary cells that have the potential to differentiate into a variety of tissue cell types (bone, cartilage, fat, practically any type of cell in the human body). A large number of mesenchymal stem cells can be harvested, eliminating the disadvantage of a long wait before their utilization. Bone marrow progenitor cells / mesenchymal stem cells open up possibilities towards growing unlimited supplies of organs.

Allogenic cells are cells harvested from the body of a donor of the same species. There are allogenic stem cells that can be used as well, and have obvious advantages, but since they are most often derived from embryonic tissue, there are a lot of ethical aspects to consider first.

Stem cells derived from embryonic tissue have an even greater potential to differentiate into other cells and tissues than stem cells derived from adult bone marrow or fat. Embryonic stem cells are derived from a human ovum/egg, fertilized or stimulated into growth in a culture medium outside the body. Undifferentiated embryonic stem cells are taken from the center of the blastocyst (a stage of development of the egg; a blastocyst contains several hundred cells). Another stem cell source is the umbilical cord blood; even though cells taken from umbilical cord blood are not as versatile as embryonic stem cells, and not as numerous, their use is less controversial, just as the use of stem cells taken from adults.

Xenogenic cells are another option. These are cells isolated from individuals of another species. Animal cells have been used quite extensively in attempts to create cardiovascular implants. Xenogenic cells are suitable for use in combination with immunosuppressive drugs. The possibility of breeding animals whose tissues would be immunologically accepted in humans is also being investigated. However, this option would raise ethical concerns. Researchers are also seeking to generate human organs in animals (xenotransplantation); there is research concentrating on genetically engineering pigs to provide organs that would not pose immunorejection problems to humans. However, there's a small risk of viral transfer from animals to humans. Pig organs are currently used for short-term ?bridge � transplants; patients may wait safely until a human donor organ or other form of therapy becomes available.

To resume, tissue engineering has its advantages and disadvantages. The solutions it provides are long-term, much safer than other options and cost-effective as well. The traditional transplantation complications are minimized, and the donor can be the patient himself/herself. The need for donor tissue is minimal, and the elimination of immunosuppression problems is a great advantage. The presence of residual foreign material is eliminated as well.

The obstacles or challenges tissue engineering has to face are related to cell isolation and preparation, to biomaterial design, to the optimization of nutrient transport and to transplantation complexity. Active seeding presents some technical difficulties, and there may be obstacles to growing cells in sufficient quantities, to urging their differentiation into the desired cell type and to ensuring their blood and nutrient supply after implantation in the body.

The difficulties tissue engineering scientists may encounter include the unavailability of autologous cells, the time necessary for cells to develop in culture before they can be used, and possible lack of function at the donor site. The ethical controversies surrounding the harvesting of cells from embryonic sources should not be overlooked. People who believe life starts at conception find it hard to accept that human ova be destroyed for embryonic stem cell production. Another ethical dilemma surrounds therapeutic cloning, another technique used to produce stem cells that can also be employed towards the production of clones of beings. Most legitimate scientists reject the use of stem cell research for such purposes. There are ethical concerns about xenotransplantation as well; the use of animals for tissue or organ generation is a delicate issue.

Even so, great progress has been made in tissue engineering research, and even greater possibilities have been opened up for the future, including the creation of entire body organs. The key applications of tissue engineering have been, firstly, the creation of dermal tissue combined with a synthetic epidermal layer, to be used for wound repair until sufficient amounts of the patient's own skin are available for grafting, and, secondly, living human skin tissue, used to test skin care, chemical and pharmaceutical products for all sorts of indications. Both mechanical and tissue prosthetic heart valves have been created, as well as tissue-engineered blood vessels without synthetic or exogenous materials. Cartilage tissue for surgical procedures has been developed, and the creation of ?bone-on-demand � is being currently pursued; scientists are trying to concentrate bone morphogenetic protein (BMP) complex locally, to stimulate bone formation when and where needed. Much research focuses on the creation of cardiac tissue to replace scar tissue after a myocardial infarction.

The growth of blood and blood products in the laboratory will soon supply cells for the therapy of blood disease such as haemophilia. Promising artificial nerve grafts are being developed for peripheral nerve regeneration, as well as nerve guidance channels to bridge the gap between damaged nerve ends. Another success has been the creation of a lung bud in culture, up to the stage of branching morphogenesis; its successful implantation and growth in-vivo would mean the elimination of typical organ transplantation problems.

The development of artificial organs is one of the main focus points for future research; a good matrix system for the development of an artificial liver is under research. The transplantation of healthy insulin-secreting islets into the pancreas is used in the treatment of one of the diabetes types, but researchers are trying to produce genetically engineered cells that overproduce insulin as well. There is also much future hope about the development of artificial human thyroid tissues, capable of producing T-cells. Even treatment of sleep disorders is investigated in tissue engineering; there is hope to reverse some of the symptoms of narcolepsy by transplantation of engineered cells to replace missing hypocretin/orexin-producing neurons in the brain.

Leaders in the field, such as Joseph Vacanti and Robert Langer, say that we are only at the beginning of a 30-year process that will lead to the effective repair and replacement of human organs. Indeed, research in the field has fully indicated that tissue engineering is able to provide alternatives for improving health and the quality of life. Given the medical and market potential of this relatively new science, there is ever-growing interest, both academic and corporate, in its technologies. Therefore, necessity has arisen that safety and efficacy standards be established, such as quality control and evaluation standards, regulations regarding the sourcing of cells and tissues, the characterization and testing of materials, as well as preclinical and clinical evaluation. Cohesive strategies that should encompass all stem cell research are necessary.